Réaction #1857596

Équation de réaction

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride

3-methoxybenzoic acid

EDC

triethyl amine

→

N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-3-methoxybenzamide

Rendement 43.6%

Solvants

DCM

DCM

Conditions de réaction

Traitement

1. 1
   Lavagethe organic phase was washed with aqueous 0.1 N HCL (150 mL)
2. 2
   SéchageThe organic layer was dried over sodium sulfate
3. 3
   Filtrationfiltered
4. 4
   Concentrationconcentrated on the rotovap
5. 5
   AutreThe crude product was purified by silica gel chromotography (40% ethyl acetate in hexanes)
6. 6
   Autreto afford 225 mg of an off white solid
7. 7
   AutreThe solid was triturated with ethyl acetate/hexanes (1/9)
8. 8
   Filtrationthe white solid was collect by filtration
9. 9
   workup.DISSOLUTIONThe pure product was dissolved in absolute ethanol
10. 10
    Concentrationconcentrated on the rotovap (4×, 25 mL)

Mode opératoire

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride (Example 4-1a) (300 mg, 1.3 mmol), 3-methoxybenzoic acid (172 mg, 1.3 mmol), EDC (386 mg, 2 mmol), and triethyl amine (303 mg, 3 mmol) were stirred in DCM (5 mL) at ambient temperature for 6 hours. The reaction was diluted with DCM (50 mL) and the organic phase was washed with aqueous 0.1 N HCL (150 mL) followed by aqueous 1N NaOH (150 mL). The organic layer was dried over sodium sulfate, filtered and concentrated on the rotovap. The crude product was purified by silica gel chromotography (40% ethyl acetate in hexanes) to afford 225 mg of an off white solid. The solid was triturated with ethyl acetate/hexanes (1/9) and the white solid was collect by filtration. The pure product was dissolved in absolute ethanol and concentrated on the rotovap (4×, 25 mL) to afford N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-3-methoxybenzamide (185 mg, 43%) as a white solid. NMR (CDCl3, 400 MHz): b 2.20 (s, 3H), 2.42 (s, 3H), 3.85 (s, 3H), 5.03 (s, 2H), 7.09-7.06 (m, 1H), 7.37-7.35 (m, 2H), 7.41 (m, 1H), 7.51 (s, 1H), 7.93 (bs, 1H), 8.03 (s, 1H). LC/MS; [M+H] calculated for C17H18N4O3; expected 327.14. Found 327.30. Melting point: 127-129° C.

Source